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22-04-2024 | Underweight | REVIEW

The Impact of Non-bone Metastatic Cancer on Musculoskeletal Health

Authors: Fabiola Galiana-Melendez, Joshua R. Huot

Published in: Current Osteoporosis Reports

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Abstract

Purpose of Review

The purpose of this review is to discuss the musculoskeletal consequences of cancer, including those that occur in the absence of bone metastases.

Recent Findings

Cancer patients frequently develop cachexia, a debilitating condition reflected by weight loss and skeletal muscle wasting. The negative effects that tumors exert on bone health represents a growing interest amongst cachexia researchers. Recent clinical and pre-clinical evidence demonstrates cancer-induced bone loss, even in the absence of skeletal metastases. Together with muscle wasting, losses in bone demonstrates the impact of cancer on the musculoskeletal system. Identifying therapeutic targets that comprehensively protect musculoskeletal health is essential to improve the quality of life in cancer patients and survivors.

Summary

IL-6, RANKL, PTHrP, sclerostin, and TGF-β superfamily members represent potential targets to counteract cachexia. However, more research is needed to determine the efficacy of these targets in protecting both skeletal muscle and bone.
Literature
9.
go back to reference Gullett N, Rossi P, Kucuk O, Johnstone PA. Cancer-induced cachexia: a guide for the oncologist. J Soc Integr Oncol. 2009;7(4):155–69.PubMed Gullett N, Rossi P, Kucuk O, Johnstone PA. Cancer-induced cachexia: a guide for the oncologist. J Soc Integr Oncol. 2009;7(4):155–69.PubMed
19.
go back to reference Couderc AL, Liuu E, Boudou-Rouquette P, Poisson J, Frelaut M, Montegut C, et al. Pre-Therapeutic Sarcopenia among Cancer Patients: An Up-to-Date Meta-Analysis of Prevalence and Predictive Value during Cancer Treatment. Nutrients. 2023;15(5):1193. https://doi.org/10.3390/nu15051193. Couderc AL, Liuu E, Boudou-Rouquette P, Poisson J, Frelaut M, Montegut C, et al. Pre-Therapeutic Sarcopenia among Cancer Patients: An Up-to-Date Meta-Analysis of Prevalence and Predictive Value during Cancer Treatment. Nutrients. 2023;15(5):1193. https://​doi.​org/​10.​3390/​nu15051193.
23.
28.
go back to reference Zaheer S, LeBoff MS. Osteoporosis: Prevention and Treatment. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al., editors. Endotext. South Dartmouth (MA):MDText.com, Inc.; 2000. Zaheer S, LeBoff MS. Osteoporosis: Prevention and Treatment. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al., editors. Endotext. South Dartmouth (MA):MDText.com, Inc.; 2000.
35.
go back to reference •• Cameron ME, Underwood PW, Williams IE, George TJ, Judge SM, Yarrow JF, et al. Osteopenia is associated with wasting in pancreatic adenocarcinoma and predicts survival after surgery. Cancer Med. 2022;11(1):50–60. https://doi.org/10.1002/cam4.4416. An important study which demonstrated that osteopenia was the strongest predictor of survival in patients with pancreatic cancer.CrossRefPubMed •• Cameron ME, Underwood PW, Williams IE, George TJ, Judge SM, Yarrow JF, et al. Osteopenia is associated with wasting in pancreatic adenocarcinoma and predicts survival after surgery. Cancer Med. 2022;11(1):50–60. https://​doi.​org/​10.​1002/​cam4.​4416. An important study which demonstrated that osteopenia was the strongest predictor of survival in patients with pancreatic cancer.CrossRefPubMed
41.
go back to reference Clemente-Suarez VJ, Redondo-Florez L, Rubio-Zarapuz A, Martinez-Guardado I, Navarro-Jimenez E, Tornero-Aguilera JF. Nutritional and Exercise Interventions in Cancer-Related Cachexia: An Extensive Narrative Review. Int J Environ Res Public Health. 2022;19(8):4604. https://doi.org/10.3390/ijerph19084604. Clemente-Suarez VJ, Redondo-Florez L, Rubio-Zarapuz A, Martinez-Guardado I, Navarro-Jimenez E, Tornero-Aguilera JF. Nutritional and Exercise Interventions in Cancer-Related Cachexia: An Extensive Narrative Review. Int J Environ Res Public Health. 2022;19(8):4604. https://​doi.​org/​10.​3390/​ijerph19084604.
53.
go back to reference Huot JR, Pin F, Bonetto A. Muscle weakness caused by cancer and chemotherapy is associated with loss of motor unit connectivity. Am J Cancer Res. 2021;11(6):2990–3001.PubMedPubMedCentral Huot JR, Pin F, Bonetto A. Muscle weakness caused by cancer and chemotherapy is associated with loss of motor unit connectivity. Am J Cancer Res. 2021;11(6):2990–3001.PubMedPubMedCentral
57.
go back to reference • Pin F, Jones AJ, Huot JR, Narasimhan A, Zimmers TA, Bonewald LF, Bonetto A. RANKL Blockade Reduces Cachexia and Bone Loss Induced by Non-Metastatic Ovarian Cancer in Mice. J Bone Miner Res. 2022;37(3):381–96. https://doi.org/10.1002/jbmr.4480. This study shows that targeting RANKL preserves musculoskeletal health in a mouse model of ovarian cancer.CrossRefPubMed • Pin F, Jones AJ, Huot JR, Narasimhan A, Zimmers TA, Bonewald LF, Bonetto A. RANKL Blockade Reduces Cachexia and Bone Loss Induced by Non-Metastatic Ovarian Cancer in Mice. J Bone Miner Res. 2022;37(3):381–96. https://​doi.​org/​10.​1002/​jbmr.​4480. This study shows that targeting RANKL preserves musculoskeletal health in a mouse model of ovarian cancer.CrossRefPubMed
60.
go back to reference • Delfinis LJ, Bellissimo CA, Gandhi S, DiBenedetto SN, Garibotti MC, Thuhan AK, et al. Muscle weakness precedes atrophy during cancer cachexia and is linked to muscle-specific mitochondrial stress. JCI Insight. 2022;7(24). https://doi.org/10.1172/jci.insight.155147.An interesting study suggesting that cancer-induced muscle weakness occurs prior to the onset of cancer-induced muscle wasting. • Delfinis LJ, Bellissimo CA, Gandhi S, DiBenedetto SN, Garibotti MC, Thuhan AK, et al. Muscle weakness precedes atrophy during cancer cachexia and is linked to muscle-specific mitochondrial stress. JCI Insight. 2022;7(24). https://​doi.​org/​10.​1172/​jci.​insight.​155147.​An interesting study suggesting that cancer-induced muscle weakness occurs prior to the onset of cancer-induced muscle wasting.
78.
go back to reference Kays JK, Koniaris LG, Cooper CA, Pili R, Jiang G, Liu Y, Zimmers TA. The Combination of Low Skeletal Muscle Mass and High Tumor Interleukin-6 Associates with Decreased Survival in Clear Cell Renal Cell Carcinoma. Cancers (Basel). 2020;12(6). https://doi.org/10.3390/cancers12061605. Kays JK, Koniaris LG, Cooper CA, Pili R, Jiang G, Liu Y, Zimmers TA. The Combination of Low Skeletal Muscle Mass and High Tumor Interleukin-6 Associates with Decreased Survival in Clear Cell Renal Cell Carcinoma. Cancers (Basel). 2020;12(6). https://​doi.​org/​10.​3390/​cancers12061605.
88.
113.
go back to reference Onuma E, Tsunenari T, Saito H, Sato K, Yamada-Okabe H, Ogata E. Parathyroid hormone-related protein (PTHrP) as a causative factor of cancer-associated wasting: possible involvement of PTHrP in the repression of locomotor activity in rats bearing human tumor xenografts. Int J Cancer. 2005;116(3):471–8. https://doi.org/10.1002/ijc.21038.CrossRefPubMed Onuma E, Tsunenari T, Saito H, Sato K, Yamada-Okabe H, Ogata E. Parathyroid hormone-related protein (PTHrP) as a causative factor of cancer-associated wasting: possible involvement of PTHrP in the repression of locomotor activity in rats bearing human tumor xenografts. Int J Cancer. 2005;116(3):471–8. https://​doi.​org/​10.​1002/​ijc.​21038.CrossRefPubMed
116.
go back to reference Atkins GJ, Rowe PS, Lim HP, Welldon KJ, Ormsby R, Wijenayaka AR, et al. Sclerostin is a locally acting regulator of late-osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE-ASARM-dependent mechanism. J Bone Miner Res. 2011;26(7):1425–36. https://doi.org/10.1002/jbmr.345.CrossRefPubMed Atkins GJ, Rowe PS, Lim HP, Welldon KJ, Ormsby R, Wijenayaka AR, et al. Sclerostin is a locally acting regulator of late-osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE-ASARM-dependent mechanism. J Bone Miner Res. 2011;26(7):1425–36. https://​doi.​org/​10.​1002/​jbmr.​345.CrossRefPubMed
118.
go back to reference Terpos E, Christoulas D, Katodritou E, Bratengeier C, Gkotzamanidou M, Michalis E, et al. Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: reduction post-bortezomib monotherapy. Int J Cancer. 2012;131(6):1466–71. https://doi.org/10.1002/ijc.27342.CrossRefPubMed Terpos E, Christoulas D, Katodritou E, Bratengeier C, Gkotzamanidou M, Michalis E, et al. Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: reduction post-bortezomib monotherapy. Int J Cancer. 2012;131(6):1466–71. https://​doi.​org/​10.​1002/​ijc.​27342.CrossRefPubMed
124.
go back to reference Bonewald LF, Mundy GR. Role of transforming growth factor-beta in bone remodeling. Clin Orthop Relat Res. 1990;250:261–76.CrossRef Bonewald LF, Mundy GR. Role of transforming growth factor-beta in bone remodeling. Clin Orthop Relat Res. 1990;250:261–76.CrossRef
Metadata
Title
The Impact of Non-bone Metastatic Cancer on Musculoskeletal Health
Authors
Fabiola Galiana-Melendez
Joshua R. Huot
Publication date
22-04-2024
Publisher
Springer US
Published in
Current Osteoporosis Reports
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-024-00872-4